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Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression.
Jordan P Steinberg; Kogo Takamiya; Ying Shen; Jun Xia; Maria E Rubio; Sandy Yu; Wenying Jin; Gareth M Thomas; David J Linden; Richard L Huganir (Profiled Authors: Richard Huganir; David Linden; Kogo Takamiya; Gareth Thomas)
Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Cerebellar long-term depression (LTD) is a major form of synaptic plasticity that is thought to be critical for certain types of motor learning. Phosphorylation of the AMPA receptor subunit GluR2 on serine-880 as well as interaction of GluR2 with PICK1 have been suggested to contribute to the endocytic removal of postsynaptic AMPA receptors during LTD. Here, we show that targeted mutation of PICK1, the GluR2 C-terminal PDZ ligand, or the GluR2 PKC phosphorylation site eliminates cerebellar LTD in mice. LTD can be rescued in cerebellar cultures from mice lacking PICK1 by transfection of wild-type PICK1 but not by a PDZ mutant or a BAR domain mutant deficient in lipid binding, indicating the importance of these domains in PICK1 function. These results demonstrate that PICK1-GluR2 PDZ-based interactions and GluR2 phosphorylation are required for LTD expression in the cerebellum.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
ShiYong Huang; Mario Treviño; Kaiwen He; Alvaro Ardiles; Roberto de Pasquale; Yatu Guo; Adrian Palacios; Richard Huganir; Alfredo KirkwoodNeuron 2012;73(3):497-510.
Hee Jung Chung; Jordan P Steinberg; Richard L Huganir; David J LindenScience (New York, N.Y.) 2003;300(5626):1751-5.
D J LindenProceedings of the National Academy of Sciences of the United States of America 2001;98(24):14066-71.
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